Phosphatidylserine

Description

Phosphatidylserine (PS) is a naturally occurring phopspholipid that appears to play an important role in the function of brain cells, including neurotransmitter function and synaptic communication.

Until recently it was only available as a supplement in the form of a bovine extract, which is unacceptable to many vegetarian consumers and others fearing viral disease. Early studies used the bovine resource, usually identified as BC-PS (Bovine cortex phosphatidyleserine).

PS was known to occur naturally in soy as the phospholipid lecithin but only now is this commercially available. It is provided to a number of vitamin/supplement manufacturing companies. The equivalence of the two products has been indicated in studies by Gindin.

The outer membrane of brain cells is composed of a double layer of phosphatides, with their heads facing out and their tails facing in. In healthy cells, PS is almost always concentrated in the inner layer, except in certain types of communication between two cells that are touching or from the cell to nearby cells, where PS flips to the outer layer and becomes part of a "vesicle" that carries a chemical message.

PS is a phospholipid which serves to bind the diversity of other large molecules, forming the cell membrane. The phosphatide heads each have an amino at the front end, followed by a phosphate, then by a glycerol, to which two lipid tails are attached.

Besides PS, there are 3 other phosphatides, phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI), and a different class called sphingomyelins.

Technical Specifications of Phosphatidylserine formulations

The Phosphatidylserine Formulations contain soy lecithin with high concentrations of phosphatidylserine.

Accuracy tolerance of weight per ingrediet is plus or minus 5%.

Fatty acid content of the Phosphatidylserine Formulations dry powder per 100 granls is as follows:

Fatty Acid Weight

capric acid (C6:0)	0.4 gr.
caprillic acid (C8:0)	3.6 gr.
lauric acid (Cl2:0)	0.1 gr.
palmitic acid (C16:0)	7.0 gr.
stearic acid (CI8:0)	1.5 gr.
oleic acid (CI8:1)	4.2 gr.
linoleic acid (C 1 8:2)	20.0 gr.
linolenic acid (CI8:3)	2.2 gr.

Hazard Summary: all ingredients of the products are biologically compatible and do not bear any known explicit or implicit toxic potential. The product has no fire or explosion hazard and is chemically inert.

Method of Action

Given orally, PS is rapidly absorbed and readily crosses the blood barrier (BBB) to reach the brain where it is taken up by the cell membranes.

The membranes of nerve cells are particularly high in Phosphatidylserine (PS). PS supports multiple membrane functions in nerve cells.

Human trials dating back to the 1970s support benefits to cognitive functions following the consumption of PS in the form of dietary supplements.

These include:

        conducting the nerve impulse;
        manipulating nerve transmitter substances;
        signal transduction (Zanotti);
        supporting cell homeostasis (Toffano);
        cellular detoxification;
        antioxidant effects (Latorraca).

Current interest surrounds this combination of mental abilities, the restoration of which simulates a process of rejuvenation.        

Benefits which are often mentioned for "mature adults" include (Crook), 1991:-

        learn and remember names;
        recognize acquaintances;
        recall numbers;
        concentration.


Phosphatidylserine is even being heralded as an exciting new sports nutrient! PS was shown to lower the production of stress hormones in healthy, young men subjected to exercise-induced stress, when given prior to the stress, in an open, placebo-controlled trial.

Higher dosages are involved than for older persons seeking purely cognitive benefits: Amounts up to 800 mg. PS, are taken one hour before a workout. As a precaution it is suggested that if digestive discomfort occurs, cut to 200 mg., then gradually increase to 800 mg. over several days or a few weeks, if tolerable.

It is often wise to progress in this fashion rather than to "jump in the deep end" straight away.





        

Therapeutic Approaches

Indications

Nutritional support for memory, learning, and emotional well-being, by protecting against age-related disturbances of neurotransmitter systems, loss of normal metabolism levels in the brain, loss of nerve connections (synapses) in the brain, and impairment of various higher mental activities.

Also, nutritional support for nerve cell differentiation, activation and renewal, neurotransmitter production and release, and maintaining electrical current flows in and between the cells.

Especially indicated for people over 50 years of age, and for people who may have prematurely damaged brain cell membranes due to disease, alcohol or other drug use, pollution, or other causes. May be a necessary, permanent supplement to treatment for epilepsy. Also indicated for protection against stress hormone release, a negative adaptation to stress, in adults of any age.


Suggested dosage:

One capsule (100 mg PS), three times a day with meals. Taking too close to bedtime may delay falling asleep.


Results of Clinical Trials

In double-blind clinical trials, PS has led to improvements in recognizing faces, learning and recalling names with faces; recall of numbers, misplaced objects, and written information; recall of details of recent events; alertness, and ability to concentrate while reading, tawng and performing tasks.

Other double-blind clinical trials have shown improvements in activities related to daily living, especially a lessening of apathy and withdrawal. In one of these trials, benefits lasted 3 months after stopping PS, even though only 200 mg. were taken daily during the dosage phase (the suggested use is 300 mg. daily, divided into 3 doses).

Double-blind clinical trials have included documentation of improvements in brain function using EEG; (ElectroEncephaloGraphy) and PET (Positron Emission Tomography). Intravenous PS injection in men 21 to 28 years of age boosted alpha rhythm an average of 15 to 20%, measured by EEG. Alpha rhythm is associated with acetylcholine-cholinergic activity in the brain, and is often reduced in aging and in cognitive deterioration. In other subjects with mild cognitive deterioration, 8 week dosing sessions improved EEG "powee, levels toward normal, accompanied by general clinical improvement.

In a variety of double-blind and open clinical trials, PS has consistently improved memory and functioning in elderly women, restored the daily rhythm of thyrotropin hormone (TSH) secretion, and given some benefit to women with physical complaints that apparently had a psychological basis.

In a preliminary investigation, Cocito and collaborators found evidence that permanent use of PS may be important for people with epilepsy.

Toxicity Factors

Phosphatidylserine (PS) is derived from soy phospholipids, a natural food with a long history of safe use in foods and dietary supplements for humans and animals.

Medical literature currently contains dozens of human studies. In 23 peer-reviewed human studies, PS has been shown to be safe and effective for human use.

200 mg. or more PS taken at once may (rarely) cause nausea, by stimulating an excessive release of dopamine.

300 mg. per day is associated with lower uric acid and liver SGPT levels, without adverse clinical effect. Dogs survived 70 grams daily (233 times the normal human dose) for a year without apparent histological damage.

Because no reproductive studies appear to be available, it is not recommended for use when pregnant or nursing without supervision by a knowledgeable health care practitioner.

Abstracts

References

Agren-JJ et al: Fatty acid composition of erythrocyte, platelet, and serum lipids in strict vegans. Lipids. 1995 Apr; 30(4): 365-9.

Allegro, L., V. Favaretto, and G. Ziliotto, 1987. "Oral phosphatidylserine in elderly subjects with cognitive deterioration-an open study." Clin. Trials J. 24: 104-108.

Amaducci, L., and the SMID Group, 1988. "Phosphatidylserine in the dosing of Alzheimer's disease: results of a multicenter study." Psychopharmacol. Bull. 24: 130134.

Amaducci, L., et al., 1991. Use of phosphatidylserine in Alzheimer’s Disease. Ann. N.Y. Acad. Sci. 640:245-249.

Aporti, F., et al., 1986. "Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine." Neurobiology of Aging 7: 115-120.

Argentiero, V., and B. Tavolato, 1980. "Dopamine (DA) and serotonin metabolic levels in the cerebrospinal fluid (CSF) in Alzheimer's presenile dementia under basic conditions and after stimulation with cerebral cortex phospholipids (BC-PL)." Journal of Neurology (Zeitschrift fur Neurologie) 224: 53-58.

Bar-Meir-E et-al: Multiple autoantibodies in patients with silicone breast implants. J-Autoimmun. 1995 Apr; 8(2): 267-77.

Barka-N et al: Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency. Clin-Diagn-Lab-Immunol. 1995 Jul; 2(4): 469-72.

Bellini-F & Bruni-A. Role of a serum phospholipase A1 in the phosphatidylserine-induced T cell inhibition. FEBS-Lett. 1993 Jan 18; 316(1): 1-4.

Bruni, A., and G. Toffano, 1982. "Lysophosphatidylserine, a short-lived intermediate with plasma membrane regulatory properties." Pharmacological Res. Comms. 14: 469484.

Caffarra, P., and V. Santamaria, 1987. "The effects of phosphatidylserine in subjects with mild cognitive decline. An open trial." Clin. Trials J. 24: 109-114.

Cenacchi, B., C. Baggio, and E. Palin, 1987. "Human tolerability of oral phosphatidylserine assessed through laboratory examinations." Clin. Trials J. 24: 125130.

Cenacchi, B., et al., 1993. "Cognitive decline in the elderly: A double-blind, placebocontrolled multicenter study on efficacy of phosphatidylserine administration." Aging Clin. Exp. Res. 5: 123-133.

Chang-CP et al: Contribution of platelet microparticle formation and granule secretion to the transmembrane migration of phosphatidylserine. J-Biol-Chem. 1993 Apr 5; 268(10): 7171-8.

Chedid-A et-al: Phospholipid antibodies in alcoholic liver disease. Hepatology. 1994 Dec; 20(6): 1465-71.

Cocito, L., et al., 1994. "GABA and phosphatidylserine in human photosensitivity: a pilot study." Epilepsy Research 17: 49-53.

Cohen, S.A., and W.E. Mueller, 1992. "Age-related alterations of NMDA-receptor properties in the mouse forebrain: partial restoration by chronic phosphatidyiserine dosing." Brain Research 584: 174-180.

Connor-J et aL: Exposure of phosphatidylserine in the outer leaflet of human red blood cells. Relationship to cell density, cell age, and clearance by mononuclear cells. J-Biol-Chem. 1994 Jan 28; 269(4): 2399-404.

Crook, T.H., et al., 1991. "Effects of phosphatidylserine in age-associated memory impairment." Neurol. 41: 644-649.

Crook, T.H., et al., 1992. "Effects of phosphatidylserine in Alzheimer's disease." Psychopharmacol. Bull. 28: 61-66.

Daleke-DL et al: Protein kinase C as a measure of transbilayer phosphatidylserine asymmetry. Anal-Biochem. 1994 Feb 15; 217(1): 33-40.

Delwaide, P.J., et al., 1986. "Double-blind randomized controlled study of phosphatidylserine in demented subjects." Acta Neurol. Scand. 73: 136-140.

Engel, R.R., et al., 1992. "Double-blind cross-over study of phosphatidylserine vs. placebo in subjects with early cognitive deterioration of the Alzheimer type." Eur. Neuropsychopharmacol. 2: 149-55.

Epand-RM et al: HDL and apolipoprotein A-I protect erythrocytes against the generation of procoagulant activity. Arterioscler-Thromb. 1994 Nov; 14(11): 1775-83.

Ermel-LD et al: Interaction of heparin with antiphospholipid antibodies (APA) from the sera of women with recurrent pregnancy loss (RPL). Am-J-Reprod-Immunol. 1995 Jan; 33(1): 14-20.

Folstein, M.F., et al., 1975. "Mini mental state." J. Psychiatric Res. 12: 189-198.

Funfgeld, E.W., et al., 1989. "Double-blind study with phosphatidylserine (PS) in Parkinsonian patients with senile dementia of Alzheimer's type (SDAT)." Progr. Clin. Biol. Res. 317: 1235-1246.

Funfgeld, E.W., and P. Nedwidek, 1987. "Neurohomologous phosphatidylserine in Parkinsonian subjects with associated disorders of cerebral metabolism." Clin. Trials J. 24: 42-61.

Gallo-P et al: Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum. SO: J-Neurol-Sci. 1994 Mar; 122(1): 97-101.

Gilbert-GE & Drinkwater-D. Specific membrane binding of factor VIII is mediated by O-phospho-L-serine, a moiety of phosphatidylserine. Biochemistry. 1993 Sep 21; 32(37): 9577-85.

Gindin, J., et al: The effect of herbal phosphatidylserine on memory and mood in community elderly. The Gerontologist, 193 (33)1: Abstract.

Gindin, J., et al: 1995. "The effect of plant phosphatidylserine on age-associated memory impairment and mood in the functioning elderly." Geriatric Institute for Education and Research, and Department of Geriatrics, Kaplan Hospital, Rehovot, Israel.

Granata, Q., and J. DiMichele, 1987. "Phosphatidylserine in elderly patients. An open trial." Clin. Trials J. 24: 99-103.

Greenspan-P et al: Association of negatively-charged phospholipids with low-density lipoprotein (LDL) increases its uptake and the deposition of cholesteryl esters by macrophages. Biochim-Biophys-Acta. 1995 Aug 3; 1257(3): 257-64.

Halpern-Z et al: Effect of phospholipids and their molecular species on cholesterol solubility and nucleation in human and model biles. Gut. 1993 Jan; 34(1): 110-5.

Heiss, W.D., et al., 1993. "Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's Disease." Annals N.Y. Acad. Sci. 695: 327-3 1.

Heiss-WD et al: Activation PET as an instrument to determine therapeutic efficacy in Alzheimer's disease. Ann-N-Y-Acad-Sci. 1993 Sep 24; 695: 327-31.

Heiss, W.D., et al., 1994. "Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's Disease." Cognitive Deterioration 5: 88-98.

Heiss-WD et al: Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer's disease. A neuropsychological, EEG, and PET investigation. Dementia. 1994 Mar-Apr; 5(2): 88-98.

Herrmann-A et al: Role of target membrane structure in fusion with influenza virus: effect of modulating erythrocyte transbilayer phospholipid distribution. Membr-Biochem. 1993 Jan-Mar; 10(1): 3-15.

Heywood, R., D.D. Cozens, and M. Richold, 1987. "Toxicology of a phosphatidylserine preparation from bovine brain (BC-PS)." Clin. Trials J. 24: 25-32.

Kent-C: Eukaryotic phospholipid biosynthesis. Annu-Rev-Biochem. 1995; 64: 315-43.

Klinkhammer, P., B. Szelies, and W.D. Heiss, 1990. "Effect of phosphatidylserine on cerebral glucose metabolism in Alzheimer's Disease." Cognitive Deterioration 1: 197201.

Kornbluth-RS: The immunological potential of apoptotic debris produced by tumor cells and during HIV infection. Immunol-Lett. 1994 Dec; 43(1-2): 125-32.

Lane-PA: Erythrocyte membrane vesicles and irreversibly sickled cells bind protein S. Am-J-Hematol. 1994 Dec; 47(4): 295-300.

Latorraca, S., et al., 1993. "Effect of phosphatidylserine on free radical susceptibility in human diploid fibroblasts." J. Neural Transmission [P-D Sect] 6: 73-77.

Ledwozyw-A & Lutnicki-K: Phospholipid asymmetry in microsomal membranes of human brain tumors. Acta-Physiol-Hung. 1993; 81(1): 37-43.

Loeb, C., et al., 1994. "Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients." Epilepsy Res. 1: 209-212.

Lou-P et al: Effects of phosphatidylserine on the oxidation of low density lipoprotein. Int-J-Biochem. 1994 Apr; 26(4): 539-45.

Lombardi, G. F., 1989. [Terapia farmacologica con fosfatidil serina in 40 pazienti ambulatoriali con sindrome demenziale senile.] Pharmacological treatment with phosphatidylserine of 40 ambulatory patients with senile dementia syndrome. Minerva Medica 80: 599-602.

Maggioni, M., et al., 1990. "Effects of phosphatidylserine therapy in geriatric subjects with depressive disorders." Acta Psychiatr. Scand. 81: 265-270.

Mahadik-SP et al: Plasma membrane phospholipid and cholesterol distribution of skin fibroblasts from drug-naive patients at the onset of psychosis. Schizophr-Res. 1994 Oct; 13(3): 239-47.

Manfredi, M., et al., 1987. "Risultati clinici della fosfatidil-serina in 40 donne affete da turbe psico-organiche, in eta climaterica e senile." La Clinica Terapeutica 120: 33-36 [English summary].

Masturzo, P., et al., 1990. "TSH circadian secretions in aged men and effect of phosphatidylserine dosing." Chronobiologia 17: 267-274.

Merchant-TE: 31P NMR phospholipid characterization of intracranial tumors. Brain-Res. 1994 Jun 27; 649(1-2): 1-6.

Michea-LF et al: Biochemical evidence for adhesion-promoting role of major intrinsic protein isolated from both normal and cataractous human lenses. Exp-Eye-Res. 1995 Sep; 61(3): 293-301.

Monteleone, P., et al., 1990. "Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans." Neuroendocrinol. 52: 243-248.

Monteleone, P., et al., 1992. "Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men." Eur. J. Clin. Pharmacol. 41: 385-388.

References N - Z

Nerozzi, D., et al., 1987. "Fosfatidilserina e disturbi della memoria nell'anziano." La Clinica Terapeutica 120: 399-404 [English summary].

Nishizuka, Y., 1984. "Turnover of inositol phospholipids and signal transduction." Science 225: 1365-1370.

Nizzo, M.C., et al., 1978. "Brain cortex phospholipids liposomes-effects on CSF HVA, 5-HIAA and on prolactin and somatotropin secretion in man." J. Neural Transmission 43: 93-102.

Nunzi, M.G., et al., 1987. "Dendritic spine loss in hippocampus of aged rats. Effect of brain phosphatidylserine administration." Neurobiology of Aging 8: 501-5 1 0.

Nunzi, M.G., et al., 1990. "Therapeutic properties of phosphatidylserine in the aging brain." In, Phospholipids: Biochemical, Pharmaceutical, and Analytical Considerations (ed. 1. Hanin and G. Pepeu). New York: Plenum Press.

Palmieri, G., et al., 1987. "Double-blind controlled trial of phosphatidylserine in subjects with senile mental deterioration." Clin. Trials J. 24: 73-83.

Papahadjopoulos, D., 1978. "Calcium-induced phase changes and fusion in natural and model membranes." In, Membrane Fusion (ed. G.Poste and G.L. Nicholson). Amsterdam: Elsevier/North-Holland.

Pepeu-G et al: The brain cholinergic system in ageing mammals. J-Reprod-Fertil-Suppl. 1993; 46: 155-62.

Pidgeon-C et al: Antiviral phospholipids. Anti-HIV drugs conjugated to the glycerobackbone of phospholipids. J-Biol-Chem. 1993 Apr 15; 268(11): 7773-8.

Pierangeli-SS et al: Are immunoglobulins with lupus anticoagulant activity specific for phospholipids? Br-J-Haematol. 1993 Sep; 85(1): 124-32.

Plutchik, R., et al., 1970. "Reliability and validity of a scale for assessing the functioning of geriatric subjects." J. Am. Geriatric Society 18: 491-500.

Pollard-HB et al: A new hypothesis for the mechanism of amyloid toxicity, based on the calcium channel activity of amyloid beta protein (A beta P) in phospholipid bilayer membranes. Ann-N-Y-Acad-Sci. 1993 Sep 24; 695: 165-8.

Puca, F.M., et al., 1987. "Exploratory trial of phosphatidylserine efficacy in mildly demented subjects." Clin. Trials J. 24: 94-98.

Ransmayr, G., et al., 1987. "Double-blind placebo-controlled trial of phosphatidylserine in elderly subjects with arteriosclerotic encephalopathy." Clin. Trials J. 24: 62-72.

Rosadini, G., et al., 1991. "Phosphatidylserine: quantitative EEG effects in healthy volunteers." Neuropsychobiology 24: 42-48.

Rote-NS et al: Expression of phosphatidylserine-dependent antigens on the surface of differentiating BeWo human choriocarcinoma cells. Am-J-Reprod-Immunol. 1995 Jan; 33(1): 114-21.

Sinforiani, E., et al., 1987. "Cognitive decline in aging brain: therapeutic approach with phosphatidylserine." Clin. Trials J. 24: 115-124.

Toffano, G., et al., 1978. "Modification of noradrenergic hypothalamic system in rat injected with phosphatidyiserine liposomes." Life Sciences 23: 1093.

Toffano, G., 1987. "The therapeutic value of phosphatidylserine effect in the aging brain." In, Lecithin: Technological, Biological, and Therapeutic Aspects (ed. 1. Hanin and G.B. Ansell), pp. 137-146. New York: Plenum Press.

Toffano, G., et al., 1987. "Pharmacokinetics of radiolabelled brain phosphatidylserine." Clin. Trials J. 24: 18-24.

Tong-XW & Xue-QM: Alterations of serum phospholipids in patients with multiple sclerosis. Chin-Med-J-Engl. 1993 Sep; 106(9): 650-4.

Toschi-V et al: Prevalence and clinical significance of antiphospholipid antibodies to noncardiolipin antigens in systemic lupus erythematosus. Haemostasis. 1993 Sep-Oct; 23(5): 275-83.

Triggiani-M et al: Differential roles for triglyceride and phospholipid pools of arachidonic acid in human lung macrophages. J-Immunol. 1994 Feb 1; 152(3): 1394-403.

Uyama-E et al: Abnormal excretion of urinary phospholipids and sulfatide in patients with mitochondrial encephalomyopathies. Biochem-Biophys-Res-Commun. 1993 Jul 15; 194(1): 266-73.

Villardita, C., et al., 1987. "Multicentre clinical trial of brain phosphatidylserine in elderly subjects with mental deterioration." Clin. Trials J. 24: 84-93.

Wang-RH; Phillips-G Jr; Medof-ME; Mold-C. Activation of the alternative complement pathway by exposure of phosphatidylethanolamine and phosphatidylserine on erythrocytes from sickle cell disease patients. J-Clin-Invest. 1993 Sep; 92(3): 1326-35.

Wilson-R & Bell-MV: Molecular species composition of glycerophospholipids from white matter of human brain. Lipids. 1993 Jan; 28(1): 13-7.

Zannoti, A., et al., 1987. "Pharmacological properties of phosphatidylserine: effects on memory function." In, Nutrients and Brain Function (ed. W.B. Essman), pp. 95-102. New York: Karger.